We have been investigating the specificity, validity, accuracy and applicability of alpha-fetoprotein estimations used for the prenatal detection of neural tube defects. Thus far, we have assayed for alpha-fetoprotein in amniotic fluid in over 7,000 cases, and have detected some 78 affected fetuses. We have also assayed maternal serum alpha-fetoprotein in about 2,000 pregnancies in order to assess the value of this approach for the prevention of these defects. The major effort in the coming year will be to further refine the alpha-fetoprotein assay and to further reduce the false positive rate (already less than 0.1%). Particular attention is now being paid the 15-20 week gestational period when maternal serum AFP may be most useful for prenatal detection of neural tube defects. Our preliminary data suggest that maternal serum alpha-fetoprotein screening will prove to be extremely valuable in the prenatal detection of neural tube defects.